The present disclosure is generally directed to the novel use of catechol-o-methyl-transferase inhibitors (COMT inhibitors) for the treatment, amelioration or prevention of impulse control disorders. An impulsive person is apt to exhibit impulsive behavior often associated with a lack of self-control.
Impulse control disorders (ICD) are characterized by the failure to resist an impulse, drive or temptation to perform an act that is harmful to the person or to others. In most cases, the individual feels an increasing sense of tension or arousal before committing the act, and then experiences pleasure, gratification, or release at the time of committing the act. After the act is performed, there may or may not be regret or guilt. ICD, therefore, have a substantial impact on individuals as well as on society.
ICD are a separate group of psychiatric disorders, listed in the “Diagnostic and Statistical Manual of Mental Disorders” (DSM-IV) of the American Psychiatric Association as a residual category consisting of impulse control disorders ‘Not Elsewhere Classified’ (NEC) and impulse control disorders ‘Not Otherwise Specified’ (NOS). The first includes: intermittent explosive disorder, pyromania, kleptomania, pathological gambling and trichotillomania. No specific disorders are mentioned in DSM-IV under the heading: “impulse control disorders NOS”, but this group is defined as “a category for disorders of impulse control that do not meet the criteria for any specific impulse control disorder or for any other mental disorder having features involving impulse control (such as borderline, antisocial, histrionic and narcissistic personality disorders)”. In the scientific and patent literature a number of such impulse control disorders, also referred to as “atypical impulse control disorders”, are described, for instance: compulsive buying disorder, binge eating and binge drinking disorders, impulsive self-injurious behavior, such as pathological skin picking, nail-biting and nose-picking, gouging, head banging and self-biting, paraphilic sexual addictions, and lack of control of a person's sexual impulses.
Patients suffering from an impulse control disorder have to date been treated by psychotherapy, behavior modification, hypnosis, relaxation therapy and administration of varied pharmaceutical preparations, the latter with little or no success. Historically, impulse control disorders have been considered refractory to known pharmacological or psychotherapeutic treatments. Therefore, a continuing need exists for agents that will be effective to treat the symptoms associated with ICD, either by eliminating or by reducing them.
In different patent and patent applications a variety of molecular mechanisms are reported to be of therapeutic value in impulse control disorders: opioid antagonists (U.S. Pat. No. 5,780,479), anticonvulsants (WO 02/43731); serotonin antagonists (US 2001/023254); 5-HT1A agonists (WO 94/13659), serotonin reuptake inhibitors (WO 92/18005), cannabinoid antagonists (US 2004/0077650), muscarinic agonists (US 2010/0120752), selected adrenergic agonists and adrenergic receptor antagonists (WO 08/51610) and heteroaryl piperdine glycine transport inhibitors (U.S. Pat. No. 7,825,135). COMT inhibitors, specifically tolcapone and entacapone, have been reported to treat certain psychiatric disorders such as schizophrenia, major depression, bipolar disorder, substance dependency and to combat cravings associated with substance abuse (US 2009/0012177). These disorders are distinct from impulse control disorders (DSM-IV).